We are interested in determining basic rules of how the mammalian nervous system develops and in defining some of the principal events through which genes guide normal neural development. Our proposed research in this area has three main objectives. Our primary objective is to determine what developmental events may underlie the genetically-associated variations we have already observed in the development of a spinal cord reflex pathway in three different inbred mouse strains. This objective will be pursued using a range of neuroanatomical prcedures including electron microscopy, radioautography and classical neurohistological stains. In addition, one aspect of this objective involves collaborative microchemical studies of the enzyme choline acetyltransferase and its neurotransmitter product, acetylcholine, in developing motor neurons. The second objective of our research is to broaden the sampled range of genetic diversity by studying spinal cord development in embryos from additional inbred mouse strains and sublines. Our initial approach here is to search for strain differences in the development of reflex movements elicited by cutaneous stimulation of the embryos. Strains will be selected on the basis of this reflex testing for detailed morphological studies. The final objective of our proposed research is to search for additional morphological relationships in embryonic mouse spinal cord which will provide a better understanding of the events underlying genetically-associated developmental variations observed previously as well as newly detected variations (Objective 2). It is anticipated that studies in the field of our proposed research will contribute to both an understanding of normal brain development and some roles of the genome in neuroembryological processes. Such knowledge should provide a necessary background for investigations of cases where genetically-associated abnormalities are the suspected basis of adult brain disorders.